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Objective   To evaluate the impact of the combination of metformin and exercise on changes in glycated hemoglobin (HbA 1c ), functional capacity, the lipid profile, quality of life, and weight.Methods   Data from a 12-week cardiovascular rehabilitation program (2014–2016) were retrospectively evaluated. Metformin exposure was determined through recorded prescriptions, and average minutes of exercise per week were computed from exercise logs. The primary outcomes were changes in HbA 1c  and functional capacity (6-minute walk test [6MWT]) over 12 weeks. The secondary outcomes were changes in the lipid profile, quality of life, and weight. Directed acyclic graphs were used to identify potential confounders, accounted for with multiple linear regression.Results   The cohort comprised 403 patients (85 metformin users, 318 non-users). The average amount of exercise was 102.7±48.7 minutes/week among metformin users and 107.7±58.1 minutes/week among non-users. Although changes in HbA 1c  were similar for both groups, the coefficient for the metformin–exercise interaction indicated significantly greater improvements in the 6MWT among metformin users. There were no between-group differences in any secondary outcomes.Conclusions   The combination of metformin and exercise led to greater gains in functional capacity than exercise alone. This combination did not appear to influence the effects of either treatment on other outcomes.

Effects of the combination of metformin and exercise on glycated hemoglobin, functional capacity, lipid profile, quality of life, and body weight